This application proposes a career development award for an Instructor in Child Neurology with scientific interest in defining visual and neurologic outcome measures in pediatric multiple sclerosis (MS). Her long-term career goal is to conduct independent clinical research that defines, validates, and applies these outcome measures to pediatric MS trials. This proposal will provide the Candidate with additional training for the refinement of study design, performance of hands-on testing, execution of data analysis, and preparation of manuscripts and future grants to support a career as an independent clinician scientist. New skills and further knowledge will be obtained through a multi-disciplinary research program that spans the fields of neurology, pediatrics, ophthalmology, radiology using three complementary approaches: 1) intensive mentorship and collaboration with senior investigators, 2) additional didactic training in biostatistics and biomedical imaging and analysis and 3) performance of original research. The development of outcome measures for adult MS trials has led to important discoveries about the pathogenesis of disease by establishing a correlation between visual loss (as captured by low-contrast letter acuity testing) and axonal and neuronal loss (as measured by structural non-invasive imaging of the retinal nerve fiber layer [RNFL] and macula using optical coherence tomography [OCT]). Visual and neurologic measures have not been rigorously studied in children, and current research has demonstrated differences in the pathogenesis of disease in children compared to adults. This proposal will accomplish the following aims: Specific Aim 1 - Define the profile of visual and neurologic function in pediatric MS and establish which measures best distinguish children with disease from controls. Specific Aim 2 - Determine how measures of visual and neurologic function reflect axonal and neuronal loss as captured by OCT, adjusting for a history of optic neuritis. Specific Aim 3 - Validate the presence or absence of axonal loss as measured by OCT using other electrophysiologic and MRI surrogates for axonal loss. These investigations will define the potential roles for these measures of visual and neurologic function and structure in pediatric MS clinical trials. The Institutions, Mentor, and Collaborators outlined in this proposal are dedicated to research and cultivating young investigators. A structured career development plan with a rigorously mentored scientific study is proposed to position the candidate for independent investigation at the end of five years. PUBLIC HEALTH RELEVANCE: Multiple sclerosis and optic neuritis are leading causes of disability and visual loss among young and middle-aged adults in the U.S. These diseases have been increasing recognized in children; however, there have been no clinical trials to date performed in children. This work will provide support for research and mentoring of a clinician scientist to develop testing methods for vision and neurologic function in children for future trias.